Intention and Causation in Medical Non-Killing: The impact of criminal law concepts on euthanasia and assisted suicide

null RAE2008

Cirurgia oral em hipocoagulados

Monografia apresentada à Universidade Fernando Pessoa para obtenção do grau de Licenciado em Medicina Dentária

Avaliação do perfil de prescrição num Serviço Hospitalar de Psiquiatria

Projeto de Pós-Graduação/Dissertação apresentado à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de Mestre em Ciências Farmacêuticas

Intervenção dos Médicos Dentistas na cessação tabágica

Projeto de Pós-Graduação/Dissertação apresentado à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de Mestre em Medicina Dentária

Revascularização pulpar

Projeto de Pós-Graduação/Dissertação apresentado à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de Mestre em Medicina Dentária

Medicação Intracanalar em Endodontia

Projeto de Pós-Graduação/Dissertação apresentado à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de Mestre em Medicina Dentária

Novos sistemas terapêuticos de administração transcutânea

Projeto de Pós-Graduação/Dissertação apresentado à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de Mestre em Ciências Farmacêuticas

A dor no período pós-cirúrgico abdominal em doentes geriátricos

A dor é uma das principais causas do sofrimento humano, comprometendo a qualidade de vida dos indivíduos, em especial o idoso que, devido aos problemas cognitivos e à elevada medicação os torna mais suscetíveis aos efeitos adversos dos medicamentos utilizados para o alívio da dor. Neste contexto, o objetivo deste estudo é avaliar a dor na pós-cirurgia abdominal em doentes geriátricos; identificar a localização e a intensidade dolorosa utilizando a Escala Numérica; analisar a dor nas dimensões sensorial, afetiva e cognitiva, utilizando o Questionário para Dor de McGill; relacionar o processo álgico com a idade, sexo, religião e tipo de abordagem cirúrgica; saber se as intervenções autónomas de enfermagem contribuem para o alívio da dor pós-operatória. Trata-se de um estudo descritivo correlacional longitudinal, com abordagem quantitativa, desenvolvido entre 14 de fevereiro e 30 de março de 2012 num Hospital no Serviço de Cirurgia Geral. A amostra constou de 30 pacientes submetidos a cirurgias abdominais. Os dados que serviram de base a este estudo foram recolhidos através da aplicação da Escala Numérica e do Questionário de Dor de McGill. Os resultados mostraram que 60% eram homens, 50% dos doentes tinham 65 e 69 anos e todos (100%), eram católicos romanos. Na primeira avaliação, 60% apresentaram dor pós-operatória moderada, 30% severa e 10% leve. Os descritores escolhidos com maior frequência foram: fisgada (90%); fina, agulhada e pontada (70%); beliscão (60%); sensível (50%); cansativa (60%) e que incomoda (50%). Nas três avaliações seguintes houve diminuição da dor severa e moderada que, aos 180 minutos era de 0% e 3% respetivamente, aumentando a percentagem de pacientes com dor leve (7%). Não encontramos relação significativa entre a variável dor pós-operatória e o sexo mas, pelo contrário, a intensidade da dor pós-operatória e a idade. O índice de dor total e sensitiva é influenciado pelo sexo. A localização da dor é influenciada pelo tipo de cirurgia, pela idade e pelo sexo. A dor pós-operatória era, principalmente, de intensidade moderada. Mesmo nos doentes a quem não foi administrado fármaco (50%), a dor foi aliviada ao longo das quatro avaliações. Desta forma, podemos inferir que as que as intervenções autónomas de enfermagem contribuem para o alívio da dor. A informação/atualização permanente dos profissionais de saúde é indispensável para que seja possível evitar ou minimizar a ocorrência de dor.

Novel insights into the role of the GABAB receptor in depression and anxiety

The GABAB receptor is a functional heterodimer comprising the GABAB1 and GABAB2 subunits, with the GABAB1 subunit displaying two major isoforms, GABAB(1a) and GABAB(1b). Preclinical findings have strongly implicated the GABAB receptor in stress-related psychiatric disorders, however, the precise contribution of the GABAB receptor in depression and anxiety disorders remains unknown. Emerging data suggest that the interaction between adverse environmental conditions, such as early life stress, and a specific genetic composition can increase the risk to develop psychiatric disorders in adulthood. This thesis investigated the role of the GABAB receptor alone or in combination with early-life stress (maternal separation), in modulating antidepressant like and anxiety-related behaviours. Pharmacological blockade of the GABAB receptor with CGP52432 had antidepressant-like behavioural effects. Moreover, mice lacking the GABAB(1b) receptor subunit isoform exhibited antidepressant-like behaviours in adulthood but anxiety-like behaviour in early-life. In response to maternal separation, GABAB(1a)-/- mice exhibited early-life stress-induced anhedonia, a core symptom of depression, while GABAB(1b)-/- mice exhibited a more resilient phenotype. Moreover, when compared with wildtype or GABAB(1a)-/- mice, GABAB(1b)-/- mice that underwent maternal separation exhibited enhanced stressinduced neuronal activation in the hippocampus and in the nucleus accumbens (NAcc), a critical area for anhedonia thus suggesting that enhanced stress-induced neuronal activation in the hippocampus and NAcc in GABAB(1b)-/- mice may be important for their antidepressant-like phenotype and their resilience to stress-induced anhedonia. Pharmacological blockade of GABAB receptor and GABAB(1b) receptor subunit isoform loss of function increased adult hippocampal cell proliferation, thus suggesting that increased hippocampal neurogenesis could be a potential mechanism for the antidepressant-like effects of GABAB receptor antagonists and GABAB(1b) receptor subunit isoform disruption. Finally, this thesis investigated whether the expression of several genes involved in hippocampal neurogenesis or the antidepressant response were altered in the mouse hippocampus following chronic treatment with a GABAB receptor antagonist.

Practice links [Issue 51, February 2013]

Practice Links is a free e-publication for practitioners working in Irish social services, voluntary and nongovernmental sectors. Practice Links was created to enable practitioners to keep up-to-date with new publications, electronic resources and conference opportunities. Issue 51 contains advice for social workers regarding the use of social media. It also contains reviews on Cognitive-­‐behavioral interventions for children who have been sexually abused and Psycho-social interventions for reducing anti-psychotic medication in care home residents.

Practice Links [Issue 53, June 2013]

Practice Links is a free e-publication for practitioners working in Irish social services, voluntary and nongovernmental sectors. Practice Links was created to enable practitioners to keep up-to-date with new publications, electronic resources and conference opportunities. Issue 53 includes reviews of research on medication for schizophrenia and the impact of housing improvements on health.

P-glycoprotein inhibition as a strategy to increase drug delivery across the blood-brain barrier: focus on antidepressants

Depression is among the leading causes of disability worldwide. Currently available antidepressant drugs have unsatisfactory efficacy, with up to 60% of depressed patients failing to respond adequately to treatment. Emerging evidence has highlighted a potential role for the efflux transporter P-glycoprotein (P-gp), expressed at the blood-brain barrier (BBB), in the aetiology of treatment-resistant depression. In this thesis, the potential of P-gp inhibition as a strategy to enhance the brain distribution and pharmacodynamic effects of antidepressant drugs was investigated. Pharmacokinetic studies demonstrated that administration of the P-gp inhibitors verapamil or cyclosporin A (CsA) enhanced the BBB transport of the antidepressants imipramine and escitalopram in vivo. Furthermore, both imipramine and escitalopram were identified as transported substrates of human P-gp in vitro. Contrastingly, human P-gp exerted no effect on the transport of four other antidepressants (amitriptyline, duloxetine, fluoxetine and mirtazapine) in vitro. Pharmacodynamic studies revealed that pre-treatment with verapamil augmented the behavioural effects of escitalopram in the tail suspension test (TST) of antidepressant-like activity in mice. Moreover, pre-treatment with CsA exacerbated the behavioural manifestation of an escitalopram-induced mouse model of serotonin syndrome, a serious adverse reaction associated with serotonergic drugs. This finding highlights the potential for unwanted side-effects which may occur due to increasing brain levels of antidepressants by P-gp inhibition, although further studies are needed to fully elucidate the mechanism(s) at play. Taken together, the research outlined in this thesis indicates that P-gp may restrict brain concentrations of escitalopram and imipramine in patients. Moreover, we show that increasing the brain distribution of an antidepressant by P-gp inhibition can result in an augmentation of antidepressant-like activity in vivo. These findings raise the possibility that P-gp inhibition may represent a potentially beneficial strategy to augment antidepressant treatment in clinical practice. Further studies are now warranted to evaluate the safety and efficacy of this approach.

Pharmacotherapy optimization in older patients by a structured clinical pharmacist assessment and intervention

Introduction: Older individuals are particularly vulnerable to potentially inappropriate prescribing (PIP), drug related problems (DRPs) and adverse drug reactions (ADRs). A number of different interventions have been proposed to address these issues. However to-date there is a paucity of well-designed trials examining the impact of such interventions. Therefore the aims of this work were to: (i) establish a baseline PIP prevalence both nationally and internationally using the STOPP, Beers and PRISCUS criteria, (ii) identify the most comprehensive method of assessing PIP in older individuals, (iii) develop a structured pharmacist intervention supported by a computer decisions support system (CDSS) and (iv) examine the impact of this intervention on prescribing and incidence of ADRs. Results: This work identified high rates of PIP across all three healthcare settings in Ireland, 84.7% in the long term care, 70.7% in secondary care and 43.3% in primary care being reported. This work identified that for a comprehensive assessment of prescribing to be undertaken, an amalgamation of all three criteria should be deployed simultaneously. High prevalences of DRPs and PIP in older hospitalised individuals were identified. With 82.0% and 76.3% of patients reported to have at least one DRP or PIP instance respectively. The structured pharmacist intervention demonstrated a positive impact on prescribing, with a significant reduction MAI scores being reported. It also resulted in the intervention patients’ having a reduced risk of experiencing an ADR when compared to the control patients (absolute risk reduction of 6.8 (95% CI 1.5% - 12.3%)) and the number needed to treat = 15 (95% CI 8 - 68). However the intervention was found to have no significant effect on length of stay or mortality rate. Conclusion: This work shows that PIP is highly prevalent in older individuals across three healthcare settings in Ireland. This work also demonstrates that a structured pharmacist intervention support by a dedicated CDSS can significantly improve the appropriateness of prescribing and reduce the incidence of ADRs in older acutely ill hospitalised individuals.

Substance misuse in young people in Ireland - a focus on benzodiazepines

Benzodiazepines are a class of drugs that are prescribed for the treatment of anxiety and insomnia. Due to the powerful tolerance that can develop as a result of sustained use, benzodiazepines can also be dependence-forming. Benzodiazepine dependence can occur from prescribed and from recreational use, and is a significant issue for young people. The consequences of benzodiazepine dependence include cognitive and learning impairment, depressive symptoms, and increased suicide risk. Despite these risks, the nature of youth benzodiazepine use has not been explored to the same extent as other drugs. A review of existing Irish literature revealed that benzodiazepines are one of the five most recreationally-used drugs among young people. Analyses of young people attending a treatment centre indicated that young attendees from urban areas were more likely to be referred to the centre because of benzodiazepines than rural attendees. Further examination of the centre’s attendees showed that regular benzodiazepine users experienced more paranoia, loss of interest in sport, and pallor than non-regular users. Analysis of benzodiazepine prescribing to young people revealed that approximately one in seven young people were prescribed benzodiazepines for periods greater than recommended by national guidelines. Young benzodiazepine users discussed in interviews that they took benzodiazepines to escape from negative feelings and that they are generally taken in a social setting. Further interviews with youth counsellors and general practitioners highlighted that both family and community attitude to benzodiazepine use can impact on a young person’s benzodiazepine usage. Suggestions for reducing benzodiazepine use such as psychological alternatives to medication, public awareness campaigns and prescribing restrictions are provided. Future research can elaborate upon this work to determine other methods of reducing youth benzodiazepine use and the damage that it causes to the young people themselves, but also to their families, their community, and society at large.

Immune and stress factors in the pathophysiology of the mdx mouse model of Duchenne Muscular Dystrophy

Duchenne Muscular Dystrophy (DMD) is a fatal multi-system neuromuscular disease caused by loss of dystrophin. The loss of dystrophin from membranes of contractile muscle cells and the dysregulation of the DAPC, induces chronic inflammation due to tissue necrosis and eventual replacement with collagen which weakens muscular force and strength. Dystrophin deficiency may cause under-diagnosed features of DMD include mood disorders such as depression and anxiety and dysfunction of the gastrointestinal tract. The first study in the thesis examined mood in the dystrophin-deficient mdx mouse model of DMD and examined the effects of the tri-cyclic antidepressant, amitriptyline on behaviours. Amitriptyline had anti-depressant and anxiolytic effects in the mdx mice possibly through effects on stress factors such as corticotrophin-releasing factor (CRF). This antidepressant also reduced skeletal muscle inflammation and caused a reduction in circulating interleukin (IL)-6 levels. In the second and third studies, we specifically blocked IL-6 signalling and used Urocortin 2, CRFR2 agonist to investigate their potential as therapeutic targets in mdx mice pathophysiology. Isometric and isotonic contractile properties of the diaphragm, were compared in mdx mice treated with anti IL-6 receptor antibodies (anti IL-6R) and/or Urocortin 2. Deficits in force production, work and power detected in mdx mice were improved with treatment. In study three I investigated contractile properties in gastrointestinal smooth muscle. As compared to wild type mice, mdx mice had slower faecal transit times, shorter colons with thickened muscle layers and increased contractile activity in response to recombinant IL-6. Blocking IL-6 signalling resulted in an increase in colon length, normalised faecal output times and a reduction in IL-6-evoked contractile activity. The findings from these studies indicate that for both diaphragm and gastrointestinal function in a dystrophin-deficient model, targeting of IL-6 and CRFR2 signalling has beneficial therapeutic effects.